The carbohydrate moiety of the transformation-sensitive glycoprotein fibronectin was previously shown to provide protection against proteolytic attack. This protective effect is localized primarily to the collagen-binding domain of the molecule, which is normallyrich in carbohydrates. If the glycosylation of fibronectin is inhibited by tunicamycin, a specific tryptic cleavage site in this domain becomes exposed. This site has been localized to a polypeptide loop structure stabilized by disulfide bonding. The effect of retinoic acid on glycosylation and fibronectin structure is also under investigation. Chondrocytes, in contrast to fibroblasts, synthesize fibronectin that includes oligosaccharides of the high-mannose type. Treatment with retinoic acid results in a conversion to the complex-type structure, with no detectable effects on polypeptide structure. This finding indicates that this vitamin can regulate the glycosylation of a specific glycoprotein. Our objective will be to map the carbohydrate residues on fibronectin more accurately, to examine the effect of early proteolytic cleavages on the function of carbohyddrate-deficient domains, to compare the effects of proteases on human and chicken fibronectins, and to complete the retinoic acid studies.